9-17143354-G-A

Position:

• chr9-17143354-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017738.4(CNTLN):​c.427G>A​(p.Val143Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTLN NM_017738.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.61

Genes affected

CNTLN (HGNC:23432): (centlein) Enables protein domain specific binding activity; protein kinase binding activity; and protein-macromolecule adaptor activity. Involved in centriole-centriole cohesion and protein localization to organelle. Located in cytosol; microtubule organizing center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15825263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTLN	NM_017738.4	c.427G>A	p.Val143Met	missense_variant	2/26	ENST00000380647.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTLN	ENST00000380647.8	c.427G>A	p.Val143Met	missense_variant	2/26	1	NM_017738.4	P1
CNTLN	ENST00000380641.4	c.427G>A	p.Val143Met	missense_variant	2/7	2
CNTLN	ENST00000484374.1	n.511G>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.427G>A (p.V143M) alteration is located in exon 2 (coding exon 2) of the CNTLN gene. This alteration results from a G to A substitution at nucleotide position 427, causing the valine (V) at amino acid position 143 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Uncertain	1.0
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	0.99	N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.30	N;N
REVEL	Benign	0.085
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.034	D;D
Polyphen		0.90	P;P
Vest4		0.35
MutPred		0.13		Loss of catalytic residue at V143 (P = 0.0923);Loss of catalytic residue at V143 (P = 0.0923);
MVP		0.040
ClinPred		0.52	D
GERP RS		4.2
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-17143352;